Dolasetron mesylate monohydrate, (2α,6α,8α,9αβ)-octahydro-3-oxo-2,6-methano-2H-quinolizin-8-yl-1H-indole-3-carboxylate monomethanesulfonate monohydrate, (referred to as DLS-MsOH-H2O) a compound having the chemical structure,

Dolasetron Mesylate monohydrate is a serotonin receptor (5-HT3) antagonist used as an antiemetic and antinauseant agent in chemo- and radiotherapies.
DLS-MsOH-H2O developed by Merrell Dow Pharmaceuticals is marketed as tablets for oral administration and as sterile solution for intravenous administration by Aventis, under the name Anzemet®.
DLS-MsOH and its monohydrate form can be prepared by a multi step synthesis, as described in EP patent No. 0339669 (“the EP '669 patent”) as illustrated in the following scheme

Accordingly, step (c) of the reaction involves oxidation with a molar equivalent of an expensive oxidizing reagent, 3-chloroperbenzoic acid (referred to as mCPBA), which transforms to 3-chlorobenzoic acid (referred to as mCBA), waste that is disposed at the end of the reaction. Removal of mCBA is problematic, hence, leading to a contaminated product. CCA-epoxide is also contaminated by other aromatic impurities, such as [(3-ClPh)C(O)O]2 (the corresponding peroxide ) in an amount of 5%. Therefore, the oxidation reaction as described above is non-economic for scale-up. Also, the reaction in steps (e) and (f) are done by using periodic acid in ethyl acetate in step (e), and water as a solvent in step (f). Since, the reagents and the reduction products have low solubility in ethylacetate; the reaction disclosed in the above patent is slower. Also, the reaction in ethylacetate is more dangerous. In addition, since two different solvents are used in steps (e) and (f), a work-up procedure, which can lead to a decomposition of the sensitive 3-methoxycarbonyl-1,5-glutardialdehyde (the product of the oxidation step), is required.
A similar process is apparently described in EP patent No. 0266730, comprising an oxidation reaction, as described in step (c) of the above scheme, to the corresponding diol, instead of to the epoxide, as apparently disclosed in EP patent No. 0339669. The diol is then transformed to DLS-base in a similar way.
Hence, there is a need in the art for an improved process for the preparation of Dolasetron salts, preferably, Dolasetron Mesylate.